Interleukin-1 beta suppresses growth hormone-induced acid-labile subunit mRNA levels and secretion in primary hepatocytes.
Cytokines are thought to mediate the catabolic states induced by infection and trauma. Recent evidence suggests that the cytokine interleukin-1 beta (IL-1 beta) directly inhibits the anabolic insulin-like growth factor (IGF)-I: growth hormone (GH) axis. The biological activity of circulating IGF is regulated by the hepatocyte derived, GH-dependent acid-labile subunit (ALS) of the 140-kDa IGF binding protein (IGFBP) complex. ALS buffers the growth and metabolic effects of the insulin-like growth factors by sequestering them in a ternary complex with IGFBP-3. To determine whether IL-1 beta has a direct effect on hepatic ALS production, we have examined its effect on ALS mRNA levels and secretion in hepatocytes under GH-induced and basal conditions. In the presence of GH (30 ng/mL) half-maximal reduction of ALS mRNA levels and secretion was induced by between 0.3-3 ng/mL rhIL-1 beta (P < 0.05). However, under basal conditions IL-1 beta had no significant effect on ALS mRNA levels, and only a slight suppression of secretion. Our study suggests that IL-1 beta regulates ALS gene expression and secretion in a way that is dependent, in part, on interaction with the GH signalling pathway.
Delhanty
P J
PJ
Department of Molecular Medicine, University of Sydney, Kolling Institute of Medical Research, St Leonards, NSW, Australia.
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D013002:Somatomedins / Q000235:genetics* / Q000378:metabolism*
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D007375:Interleukin-1; D012333:RNA, Messenger; D013002:Somatomedins; C075944:insulin-like growth factor binding protein, acid labile subunit; D013006:Growth Hormone